Passive antibody transfer studies in animal models and the observed dose- response association between passively acquired maternal antibody and development of HSV infection in the human neonate suggest that serum antibodies protect against viral challenge. With these exceptions, however, the role of serum antibodies in the natural history of herpes infections is unclear. Clinical endpoints for studies on humoral immune correlates of reactivation disease are comprised of signs or symptoms of recurrent disease and have not taken into account the effect of asymptomatic viral reactivation on serum antibody titers. Conversely, the role of serum antibody in asymptomatic HSV reactivation has not been determined. Moreover, it is known from their viral systems that local antibodies are more closely correlated with disease resolution, subclinical reinfection, and protection from reinfection than are serum antibodies. recently, we have shown that the time course and protein targets of local immune responses differ from those of humoral immune responses to genital herpes infections. We will use quantitative enzyme immunoassays (EIA) and Western blot techniques to evaluate serum and local antibody responses to individual HSV proteins in patients from Project I who have asymptomatic versus symptomatic recurrences and in those with frequent versus infrequent asymptomatic recurrences. To evaluate whether serum and local antibodies play a role in disease acquisition, we will assay sera and secretions from the exposed-infected versus exposed-uninfected neonates seen in Project II. These studies will help define host immune factors (humoral and local) which affect asymptomatic genital excretion of HSV. These data, in turn, may help develop more effective vaccination strategies involving induction of local as well are serum antibodies.